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Genomic analysis of stress response against arsenic in Caenorhabditis elegans.

Sahu SN, Lewis J, Patel I, Bozdag S, Lee JH, Sprando R, Cinar HN - PLoS ONE (2013)

Bottom Line: Arsenic, a known human carcinogen, is widely distributed around the world and found in particularly high concentrations in certain regions including Southwestern US, Eastern Europe, India, China, Taiwan and Mexico.Biological processes such as oxidative stress, and iron metabolism, which were previously reported to be involved in arsenic toxicity studies using cultured cells, experimental animals, and humans, were found to be affected in C. elegans.FastMEDUSA analysis identified cancer-related genes, particularly genes associated with leukemia, such as dnj-11, which encodes a protein orthologous to the mammalian ZRF1/MIDA1/MPP11/DNAJC2 family of ribosome-associated molecular chaperones.

View Article: PubMed Central - PubMed

Affiliation: Division of Virulence Assessment, Food and Drug Administration, Laurel, Maryland, United States of America.

ABSTRACT
Arsenic, a known human carcinogen, is widely distributed around the world and found in particularly high concentrations in certain regions including Southwestern US, Eastern Europe, India, China, Taiwan and Mexico. Chronic arsenic poisoning affects millions of people worldwide and is associated with increased risk of many diseases including arthrosclerosis, diabetes and cancer. In this study, we explored genome level global responses to high and low levels of arsenic exposure in Caenorhabditis elegans using Affymetrix expression microarrays. This experimental design allows us to do microarray analysis of dose-response relationships of global gene expression patterns. High dose (0.03%) exposure caused stronger global gene expression changes in comparison with low dose (0.003%) exposure, suggesting a positive dose-response correlation. Biological processes such as oxidative stress, and iron metabolism, which were previously reported to be involved in arsenic toxicity studies using cultured cells, experimental animals, and humans, were found to be affected in C. elegans. We performed genome-wide gene expression comparisons between our microarray data and publicly available C. elegans microarray datasets of cadmium, and sediment exposure samples of German rivers Rhine and Elbe. Bioinformatics analysis of arsenic-responsive regulatory networks were done using FastMEDUSA program. FastMEDUSA analysis identified cancer-related genes, particularly genes associated with leukemia, such as dnj-11, which encodes a protein orthologous to the mammalian ZRF1/MIDA1/MPP11/DNAJC2 family of ribosome-associated molecular chaperones. We analyzed the protective functions of several of the identified genes using RNAi. Our study indicates that C. elegans could be a substitute model to study the mechanism of metal toxicity using high-throughput expression data and bioinformatics tools such as FastMEDUSA.

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Genome-wide expression profile comparisons of C. elegans genes regulated by arsenic and river sediment toxicants.(A) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Elbe River sediment exposure, and overlap among these data. (B) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Rhine River sediment exposure, and overlap among these data. (C) Enrichment of gene ontology categories for genes differentially expressed at Elbe River sediment exposure. (D) Enrichment of gene ontology categories for genes differentially expressed at Rhine River sediment exposure.
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pone-0066431-g004: Genome-wide expression profile comparisons of C. elegans genes regulated by arsenic and river sediment toxicants.(A) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Elbe River sediment exposure, and overlap among these data. (B) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Rhine River sediment exposure, and overlap among these data. (C) Enrichment of gene ontology categories for genes differentially expressed at Elbe River sediment exposure. (D) Enrichment of gene ontology categories for genes differentially expressed at Rhine River sediment exposure.

Mentions: Arsenic is ubiquitous throughout the earth crust in different complex forms with pyrites [75], can easily dissociate from the complex and enter into ground water [1], and be taken up by microorganisms resulting in high levels of bio-availability [1], [2]. Because of these properties, arsenic is considered as an important environmental toxin. Menzel et al. used C. elegans as a bio-monitor to characterize sediment toxicity of German rivers Rhine and Elbe [76]. In that study, C. elegans were exposed to sediments of three German rivers, Danube, Rhine, Elbe; Danube being the cleanest, and Elbe is the most contaminated among the three rivers, based on chemical properties of the sediments, including arsenic levels. Using expression profile of C. elegans exposed to Danube sediment as a reference, they identified that 748 and 694 transcripts were significantly altered in Elbe and Rhine exposed animals, respectively. We wanted to address the question of how an expression profile identified against a particular pollutant, in our case arsenic, would correlate with an expression profile identified against contaminated river sediments. We found bigger overlap between global arsenic response and response to Elbe, which is the most contaminated river in this study, with higher arsenic levels (Fig. 4, Table S6, S7). These results indicate that C. elegans may be used as an environmental bio-monitor, and meta- analysis of publicly available C. elegans expression microarray data will provide a platform to gain insights into complex environmental issues.


Genomic analysis of stress response against arsenic in Caenorhabditis elegans.

Sahu SN, Lewis J, Patel I, Bozdag S, Lee JH, Sprando R, Cinar HN - PLoS ONE (2013)

Genome-wide expression profile comparisons of C. elegans genes regulated by arsenic and river sediment toxicants.(A) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Elbe River sediment exposure, and overlap among these data. (B) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Rhine River sediment exposure, and overlap among these data. (C) Enrichment of gene ontology categories for genes differentially expressed at Elbe River sediment exposure. (D) Enrichment of gene ontology categories for genes differentially expressed at Rhine River sediment exposure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722197&req=5

pone-0066431-g004: Genome-wide expression profile comparisons of C. elegans genes regulated by arsenic and river sediment toxicants.(A) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Elbe River sediment exposure, and overlap among these data. (B) A Venn diagram illustrating number of genes expressed at low and high dose arsenic exposure, Rhine River sediment exposure, and overlap among these data. (C) Enrichment of gene ontology categories for genes differentially expressed at Elbe River sediment exposure. (D) Enrichment of gene ontology categories for genes differentially expressed at Rhine River sediment exposure.
Mentions: Arsenic is ubiquitous throughout the earth crust in different complex forms with pyrites [75], can easily dissociate from the complex and enter into ground water [1], and be taken up by microorganisms resulting in high levels of bio-availability [1], [2]. Because of these properties, arsenic is considered as an important environmental toxin. Menzel et al. used C. elegans as a bio-monitor to characterize sediment toxicity of German rivers Rhine and Elbe [76]. In that study, C. elegans were exposed to sediments of three German rivers, Danube, Rhine, Elbe; Danube being the cleanest, and Elbe is the most contaminated among the three rivers, based on chemical properties of the sediments, including arsenic levels. Using expression profile of C. elegans exposed to Danube sediment as a reference, they identified that 748 and 694 transcripts were significantly altered in Elbe and Rhine exposed animals, respectively. We wanted to address the question of how an expression profile identified against a particular pollutant, in our case arsenic, would correlate with an expression profile identified against contaminated river sediments. We found bigger overlap between global arsenic response and response to Elbe, which is the most contaminated river in this study, with higher arsenic levels (Fig. 4, Table S6, S7). These results indicate that C. elegans may be used as an environmental bio-monitor, and meta- analysis of publicly available C. elegans expression microarray data will provide a platform to gain insights into complex environmental issues.

Bottom Line: Arsenic, a known human carcinogen, is widely distributed around the world and found in particularly high concentrations in certain regions including Southwestern US, Eastern Europe, India, China, Taiwan and Mexico.Biological processes such as oxidative stress, and iron metabolism, which were previously reported to be involved in arsenic toxicity studies using cultured cells, experimental animals, and humans, were found to be affected in C. elegans.FastMEDUSA analysis identified cancer-related genes, particularly genes associated with leukemia, such as dnj-11, which encodes a protein orthologous to the mammalian ZRF1/MIDA1/MPP11/DNAJC2 family of ribosome-associated molecular chaperones.

View Article: PubMed Central - PubMed

Affiliation: Division of Virulence Assessment, Food and Drug Administration, Laurel, Maryland, United States of America.

ABSTRACT
Arsenic, a known human carcinogen, is widely distributed around the world and found in particularly high concentrations in certain regions including Southwestern US, Eastern Europe, India, China, Taiwan and Mexico. Chronic arsenic poisoning affects millions of people worldwide and is associated with increased risk of many diseases including arthrosclerosis, diabetes and cancer. In this study, we explored genome level global responses to high and low levels of arsenic exposure in Caenorhabditis elegans using Affymetrix expression microarrays. This experimental design allows us to do microarray analysis of dose-response relationships of global gene expression patterns. High dose (0.03%) exposure caused stronger global gene expression changes in comparison with low dose (0.003%) exposure, suggesting a positive dose-response correlation. Biological processes such as oxidative stress, and iron metabolism, which were previously reported to be involved in arsenic toxicity studies using cultured cells, experimental animals, and humans, were found to be affected in C. elegans. We performed genome-wide gene expression comparisons between our microarray data and publicly available C. elegans microarray datasets of cadmium, and sediment exposure samples of German rivers Rhine and Elbe. Bioinformatics analysis of arsenic-responsive regulatory networks were done using FastMEDUSA program. FastMEDUSA analysis identified cancer-related genes, particularly genes associated with leukemia, such as dnj-11, which encodes a protein orthologous to the mammalian ZRF1/MIDA1/MPP11/DNAJC2 family of ribosome-associated molecular chaperones. We analyzed the protective functions of several of the identified genes using RNAi. Our study indicates that C. elegans could be a substitute model to study the mechanism of metal toxicity using high-throughput expression data and bioinformatics tools such as FastMEDUSA.

Show MeSH
Related in: MedlinePlus